EPIX BEGINS TRIAL OF PRX-03140 IN MILD ALZHEIMER'S DISEASE

Epix Pharmaceuticals has begun a Phase IIa clinical trial to further evaluate PRX-03140 as monotherapy and in combination with donepezil for the treatment of Alzheimer's disease. This trial is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of PRX-03140 administered orally once-daily for 14 days in patients with mild Alzheimer's disease who are on a stable dose of donepezil (10 mg). Data from this trial are expected in the second half of 2007.

The primary endpoints of this randomized, double-blind, multiple-ascending-dose trial are to assess the safety and tolerability of PRX-03140 administered alone and in combination with donepezil, and to measure the effect of PRX-03140 on quantitative electroencephalograms (qEEGs), including the alpha/theta ratio (a biomarker which indicates an effect on the cholinergic system in the brain). Secondary endpoints of the trial include assessing the effects of repeat doses of PRX-03140 on a battery of standardized cognitive function tests, as well as evaluating the pharmacokinetic effect of PRX-03140 on donepezil concentrations in patients with mild Alzheimer's disease.

PRX-03140 was well-tolerated in a Phase Ib trial in patients with Alzheimer's disease and in two additional Phase I clinical trials in healthy adult and elderly volunteers. In the 14-day Phase Ib clinical trial, treatment with PRX-03140 resulted in changes in brain wave activity in Alzheimer's patients that are consistent with those seen in clinical trials with currently approved drugs for Alzheimer's disease. In the Phase Ib trial treatment with PRX-03140 resulted in a statistically significant improvement in the qEEGs slow-wave pattern when compared with placebo. This trial demonstrated that PRX-03140 is active in the central nervous system.

PRX-03140 is selective for the 5-HT4 receptor in the brain. Preclinical studies have shown that it improves cognitive function and increases levels of acetylcholine, soluble amyloid precursor protein and brain-derived neurotrophic factor in regions of the brain known to be important for memory.